Beta-adrenoreceptors were classified into three classes, β1-adrenoreceptor, β2-adrenoreceptor and β3-adrenoreceptor, and it was recognized that stimulation of β1 induces an increase in the heart rate and stimulation of β2 induces a relaxation of the smooth muscle tissue, thereby resulting in lowering the blood pressure. It was also recognized that stimulation of β3 facilitates the lipolysis in adipocytes, thereby resulting in increasing the thermogenesis. Therefore, compounds having β3-agonist activity were shown to be useful as a medicine for treating and preventing diabetes, obesity and hyperlipidemia (Nature, vol. 309, pp. 163-165, 1984; Int. J. Obes. Relat. Metab. Disord., vol. 20, pp. 191-199, 1996; Drug Development Research, vol. 32, pp. 69-76, 1994; J. Clin. Invest., vol. 101, pp. 2387-2393, 1998). Recently, it was shown that β3-adrenoreceptor is expressed in the detrusor and a β3-agonist induces a relaxation of the detrusor (J. Urinol., vol. 161, pp. 680-685, 1999; J. Pharmacol. Exp. Ther., vol. 288, pp. 1367-1373, 1999). Therefore, compounds having β3-agonist activity are expected to be useful as a medicine for treating and preventing urinary incontinence.
Some compounds showing a β3-agonist activity have been known. Compounds having high selectivity or having low β1- and β2-stimulating activities are particularly required when their usefulness as a medicine is taken into consideration. This is because compounds having both β1- and β2-stimulating activities induce side effects such as increase in the heart rate and lowering of the blood pressure, as set forth above.
So far, the following compounds have been exemplified as compounds relating to β3:
the compound (BRL 37344) having the following structural formula described in EP 023385 and the literature (Drugs of the future, vol. 16, p. 797 (1991)):
the compound (CL 316,243) having the following structural formula described in EP 0455006 and the literature (J. Med. Chem., vol. 35, p. 3081 (1992)):
andthe compound having the following structural formula described in WO 94/29290:

Further, EP 0659737 discloses a variety of compounds and specifically describes as an example in Example 1 in the text of specification the compound having the following structural formula:
However, the chemical structures of the above compounds are clearly distinct from those of the claimed compounds of the present invention.
In addition, the compound described in EP 171702 and having the following structural formula:
has been known as having heart rate-increasing activity, myocardial contraction enhancement and antiobestic activity. However, this compound acts on the heart and is different from the compound of the present invention in the chemical structure and in that the former strongly acts on the heart.
Further, the compound described in JP-A-55-53262 and JP-A-58-41860 and having the following structural formula:
is known as having α,β-blocking activity, namely the effect of lowering blood pressure; and the compound described in DE 2651572 and having the following structural formula:
is known as having vasodilator action. However, these compounds are different from the compounds of the present invention in their chemical structures and intended uses.
The present inventors formerly invented compounds having excellent β3-agonist activity and disclosed compounds represented by, for example, the following structural formula in WO 97/25311.
The above compounds, however, are different from the compounds of the present invention in their chemical structures.
Further, the present inventors disclosed compounds represented by, for example, the following structural formula in WO 01/83451.
